Rotary motor based transdermal injection device

ABSTRACT

An apparatus for injectate delivery includes a cartridge, a linear actuator, a rotary motor mechanically coupled the actuator, and a controller coupled to the motor. The controller controls a linear motion of the actuator by controlling an electrical input supplied to the motor in a first interval during which the motor is stationary with the linear actuator engaged with the cartridge to displace an injectate in the cartridge, a second interval following the first interval during which the controller accelerates the motor from stationary to a first speed selected to create a jet of the injectate from the cartridge with a velocity sufficient to pierce human tissue to a subcutaneous depth, a third interval during which the controller maintains the motor at or above the first speed, and a fourth interval during which the controller decelerates the motor to a second speed to deliver the injectate at the subcutaneous depth.

CROSS REFERENCE TO RELATED APPLICATION

Under 35 USC 120, this application is a continuation of U.S. applicationSer. No. 16/129,241, filed Sep. 12, 2018, now U.S. Pat. No. 10,413,671,which claims the benefit of the priority filing date of U.S. ProvisionalApplication No. 62/557,381, filed Sep. 12, 2017, the contents of whichare hereby incorporated by reference in their entirety.

BACKGROUND

This invention relates to a rotary motor based needle-free transdermalinjection device.

Skin serves as a protective barrier to the body. In the field of modernmedicine, drugs are often delivered through the skin into thebloodstream of patients. Traditionally, this is accomplished byinsertion of a needle through the patient's skin and into a target areafor an injection. However, the use of needles present significantdrawbacks ranging from patient fear and discomfort to safety hazardsassociated with handling used needles.

Needle-free transdermal injection devices have been developed as analternative to needle-based injectors. These devices typically use ahigh pressure, narrow jet of injectate to penetrate a patient's skin,obviating the need to pierce the patient's skin with a needle. However,there remains a need for improved needle-free injection devices.

SUMMARY

In a general aspect, an apparatus for injectate delivery includes acartridge containing a volume of an injectate and an exit port, a linearactuator configured for delivery of the injectate from the exit port ofthe cartridge, the linear actuator including a linkage, a rotary motormechanically coupled to the linkage, and a controller coupled to therotary motor. The controller is configured to control a linear motion ofthe actuator in response to a control signal by controlling anelectrical input supplied to the motor in a first interval during whichthe rotary motor is stationary and the linear actuator is engaged withthe cartridge to displace the injectate therefrom, a second intervalimmediately following the first interval during which the controlleraccelerates the rotary motor from stationary to a first speed selectedto create a jet of the injectate from the cartridge with a velocity atleast sufficient to pierce human tissue to a subcutaneous depth, a thirdinterval during which the controller maintains the rotary motor at orabove the first speed, and a fourth interval during which the controllerdecelerates the rotary motor to a second speed selected to deliver thevolume of the injectate at the subcutaneous depth.

Aspects may include one or more of the following features.

The controller may be configured to deliver a sequence of injections ofthe injectate from the volume without reverse movement of the rotarymotor. The controller may be configured to deliver a sequence ofinjections of the injectate from the volume in close temporal proximityto one another. The volume may be at least one milliliter. The volumemay be not greater than about 0.5 milliliters. The volume may be notgreater than about 0.3 milliliters. The volume may be a therapeuticamount of the injectate. The injectate may be a biological drug.

The injectate may have a viscosity of at least three centipoise at atemperature between two degrees and twenty degrees Celsius. Theinjectate may have a viscosity of about three centipoise to about twohundred centipoise at a temperature between two degrees and twentydegrees Celsius. A second velocity of the jet of injectate from thecartridge during the second interval may reach at least two hundredmeters per second. The rotary motor may provide sufficient power toreach the first speed in not more than three rotations.

A duration of the second interval may be less than hundred milliseconds.A duration of the second interval is less than sixty milliseconds. Thesecond interval may be less than ten milliseconds. The linear actuatormay be bidirectionally coupled to the rotary motor and the cartridge topermit bidirectional displacement of contents of the cartridge. Theapparatus may include plurality of supercapacitors coupled to the rotarymotor and configured to provide electrical power to the rotary motorduring the second interval, the third interval and the fourth interval.The plurality of supercapacitors may be configured to charge in paralleland discharge to power the rotary motor in serial. The rotary motor andthe plurality of supercapacitors may be configured to deliver a peakpower to the linear actuator of at least two hundred Watts.

In another general aspect, an apparatus for injectate delivery includesa cartridge containing a volume of an injectate and an exit port, alinear actuator configured for delivery of the injectate from the exitport of the cartridge, the linear actuator including a linkage, a rotarymotor mechanically coupled to the linkage, and a controller coupled tothe rotary motor. The controller is configured to control a linearmotion of the actuator in response to a control signal by controlling anelectrical input supplied to the motor in a first interval during whichthe rotary motor is engaged with the cartridge to displace the injectatetherefrom, a second interval immediately following the first intervalduring which the controller drives the rotary motor at a first speedselected to create a jet of the injectate from the cartridge with avelocity at least sufficient to pierce human tissue, a third intervalduring which the controller continues operating the motor at or abovethe first speed in order to maintain the jet of the injectate at orabove the velocity and create a channel through the human tissue to asubcutaneous depth, and a fourth interval during which the controllerdecelerates the rotary motor to a second speed selected to deliver thevolume of the injectate at the subcutaneous depth.

Aspects may include one or more of the following features.

The apparatus may include a sensor system configured to detect when theapparatus is properly positioned to deliver the injectate to a patient,wherein the controller and the rotary motor are configured to initiatedelivery of the injectate without substantial observable latency whenthe apparatus is properly positioned. The sensor system may detect acontact of the apparatus with a skin of the patient. The sensor systemmay detect an angle of the cartridge relative to a skin of the patient.The sensory system may detect a position of the exit port relative to abody of the patient.

The capacitive energy storage element may include one or moresupercapacitive energy storage elements. The one or more supercapacitiveenergy storage elements may include a plurality of supercapacitiveenergy storage elements and the supply circuitry is configured to switchthe plurality of supercapacitive energy storage elements into a parallelconfiguration during a charging operation and to switch the plurality ofsupercapacitive energy storage elements into a serial configuration foran injection operation. The capacitive energy storage element mayinclude a plurality of capacitors. The supply circuitry may beconfigured to switch the plurality of capacitors into a parallelconfiguration with the battery during a charging operation and to switchthe plurality of capacitors into a serial configuration for an injectionoperation.

The supply circuitry may include a direct current to direct current(DC/DC) converter disposed between the battery and the capacitive energystorage element. The DC/DC converter may be configured to boost avoltage supplied by the battery by a factor in a range of 5-20.Substantially all of an electrical power supplied to the rotary motorduring the second time interval and the third time interval may besupplied from the capacitive energy storage element. The injectioncontroller may be configured to prevent multiple injectate deliveryoperations within a predetermined minimum injection cycle time. In someexamples, the supply circuitry includes a DC/DC converter disposedbetween the capacitive energy storage element and the rotary motor.

The third time interval may be in a range of two to twenty times as longas the second time interval. The second time interval may have a firstduration of between 30 milliseconds and 100 milliseconds and third timeinterval has a second duration of between 100 milliseconds and 1000milliseconds.

The apparatus may include a cartridge removably and replaceably coupledto the apparatus, the cartridge containing an injectate and thecartridge including an exit port with a predetermined shape for ejectingthe injectate in a stream. The electrical input supplied during thesecond time interval may be selected to drive the rotary motor at aspeed sufficient to drive the stream from the exit port at a velocity topierce human skin, and wherein a duration of the second time interval isselected to pierce the human skin with the stream to a subcutaneousdepth. The electrical input supplied during the third time interval maybe selected to deliver additional injectate from the cartridge at thesubcutaneous depth.

Aspects may have one or more of the following advantages.

Use of an actively controlled rotary motor to drive a plunger into acartridge allows for a rapid acceleration of the plunger into thecartridge. By rapidly accelerating the plunger into the cartridge, apiercing jet with high velocity is quickly attained. Use ofsupercapacitors in the power supply supports the rapid acceleration ofthe plunger since supercapacitors have capacitance values much higherthan other capacitors and are able to store 10 to 100 times more energyper unit volume or mass than electrolytic capacitors. Supercapacitorscan also accept and deliver charge much faster than batteries, andtolerate many more charge and discharge cycles than rechargeablebatteries.

Other features and advantages of the invention are apparent from thefollowing description, and from the claims.

DESCRIPTION OF DRAWINGS

FIG. 1 is a schematic diagram of a controllable, needle-free transdermalinjection device.

FIG. 2 is a cut-away diagram of a ball screw actuator.

FIG. 3 is a block diagram of the controllable, needle-free transdermalinjection device of FIG. 1.

FIG. 4 is a detailed block diagram of the controllable, needle-freetransdermal injection device of FIG. 1.

FIG. 5 is a detailed block diagram of the power supply of thecontrollable, needle-free transdermal injection device of FIG. 1.

FIG. 6 is a target displacement profile.

FIG. 7 is a rotary motor speed profile associated with the targetdisplacement profile of FIG. 6.

FIG. 8 is an injectate jet velocity profile associated with the targetdisplacement profile of FIG. 6.

DESCRIPTION

In the following document, references to items in the singular should beunderstood to include items in the plural, and vice versa, unlessexplicitly stated otherwise or clear from the text. Grammaticalconjunctions are intended to express any and all disjunctive andconjunctive combinations of conjoined clauses, sentences, words, and thelike, unless otherwise stated or clear from the context. Thus, the term“or” should generally be understood to mean “and/or” and so forth.

Recitation of ranges of values herein are not intended to be limiting,referring instead individually to any and all values falling within therange, unless otherwise indicated, and each separate value within such arange is incorporated into the specification as if it were individuallyrecited herein. The words “about,” “approximately” or the like, whenaccompanying a numerical value or physical property, are to be construedas indicating a deviation as would be appreciated by one of ordinaryskill in the art to operate satisfactorily for an intended purpose.Similarly, words of approximation such as “approximately” or“substantially” when used in reference to physical characteristics,should be understood to contemplate a range of deviations that would beappreciated by one of ordinary skill in the art to operatesatisfactorily for a corresponding use, function, purpose or the like.Ranges of values and/or numeric values are provided herein as examplesonly, and do not constitute a limitation on the scope of the describedembodiments unless explicitly stated otherwise. The use of any and allexamples, or exemplary language (“e.g.,” “such as,” or the like)provided herein, is intended merely to better illuminate the embodimentsand does not pose a limitation on the scope of the embodiments. Nolanguage in the specification should be construed as indicating anyunclaimed element as essential to the practice of the embodiments.

In the following description, it is understood that terms such as“first,” “second,” “top,” “bottom,” “up,” “down,” and the like, arewords of convenience and are not to be construed as limiting terms.

1 Needle-Free Transdermal Injection Device

Referring to FIG. 1, a controllable, needle-free transdermal injectiondevice 100 for transferring an injectate (e.g., a drug or a vaccine inany one of a number of states such as a liquid state or a powder state)through the skin of a patient includes a needle-free transdermalinjector head 104 extending from a housing 102. The injector head 104includes a chamber 106 for holding the injectate and a nozzle 108disposed at a distal end 110 of the injector head 104. The nozzle 108includes a head 112 and an opening 114 from which a jet of the injectateis discharged from the chamber 106. In operation, the opening 114 isplaced near or against the skin 115 when the injectate is discharged.

The dimensions of the nozzle 108 may be adapted to control a shape andpressure profile of a stream of injectate exiting the nozzle 108. Forexample, the inner diameter of the opening 114 may be in a range of 50μm to 300 μm, and may employ a taper along the longitudinal axis 122toward the opening to shape an exiting stream of injectate. It will alsobe appreciated that the geometry of the chamber 106 relative to theopening 114 may affect how linear motion of a plunger or the like withinthe chamber 106 translates into an exit velocity or pressure by aninjectate through the opening 114. An outer diameter of the head 112 ofthe nozzle 108 may narrow to the opening 114, or may remain uniform ormay expand to provide a suitable resting surface for the head 112 of thenozzle 108. The nozzle 108 may have a length along the longitudinal axis122 of about 500 μm to about 5 mm. Similarly, the chamber 106 may haveany suitable length along the longitudinal axis for containing aninjectate, and for displacing the injectate through the opening 114 inone or more needle-free injections.

The chamber 106 may have a proximal end 116 and a distal end 110. Anactuator (i.e., a piston or plunger 120) may be slidably disposed withinthe chamber 106. Movement of the plunger 120 along a longitudinal axis122 in either direction can affect the pressure within chamber 106. Insome embodiments, the chamber 106 is integral to the device 100. Inother embodiments, the chamber 106 is separately attachable to device100.

In some examples, the injection device 100 includes a sensor 107 (e.g.,a mechanical sensor or a capacitive sensor) for detecting a contactbetween the apparatus and the skin of a patient. In some examples, thesensor 107 is configured to detect an angle of the cartridge relative tothe skin of the patient. In some examples, the sensor 107 is configuredto detect a position of the injection opening relative to the patient'sskin 115 or body. In some examples, the sensor 107 communicates with theinjection controller 100 to prevent injection from occurring when theapparatus is not in contact with the patient's skin 115 or when an angleor position of the apparatus relative to the patient is incorrect.

1.1 Rotary Motor

The injection device 100 may include an electromagnetic rotary motor 126that applies a force to the plunger 120 via a linkage 130 to inject theinjectate in the chamber 106 through the skin 115. The linkage mayinclude a ball screw actuator 130, and the linkage may also or insteadinclude any other suitable mechanical coupling for transferring a rotaryforce of the rotary motor 126 into a linear force suitable fordisplacing injectate from the chamber 106. For example, the linkage mayinclude one or more of lead screws, linear motion bearings, and wormdrives, or another other suitable mechanical components or combinationof mechanical components. As noted above, linear motion may usefully beinferred from rotation of a lead screw or the like, and the injectiondevice 100 may be instrumented to monitor rotation in order to providefeedback on a position of the plunger 120 to a controller during aninjection.

Referring to FIG. 2, one example of a ball screw actuator 130 includes ascrew 332 and a nut 334 (which is coupled to the housing 102 in FIG. 1),each with matching helical grooves 336. The ball screw actuator 130 mayinclude a recirculating ball screw with a number of miniature balls 338or similar bearings or the like that recirculate through the grooves 336and provide rolling contact between the nut 334 and the screw 332. Thenut 334 may include a return system 333 and a deflector (not shown)which, when the screw 332 or nut 334 rotates, deflects the miniatureballs 338 into the return system. The balls 338 travel through thereturn system to the opposite end of the nut 334 in a continuous path.The balls 338 then exit from the ball return system into the grooves336. In this way, the balls 338 continuously recirculate in a closedcircuit as the screw 332 moves relative to the nut 334.

In some examples, the rotary motor 126 is of a type selected from avariety of rotational electrical motors (e.g., a brushless DC motor).The rotary motor 126 is configured to move the screw 332 of the ballscrew actuator 130 back and forth along the longitudinal axis 122 byapplying a torque (i.e., τ_(M)) to either the screw 332 or the nut 334of the ball screw actuator. The torque causes rotation of either thescrew 332 or the nut 334, which in turn causes an input force F_(M)(t),which is proportional to the torque applied by the motor, to be appliedto the screw 332.

The torque τ_(M) applied to the screw 332 causes application of a forceF_(P) to the plunger 120 which in turn causes movement of the plunger120 along the longitudinal axis 122. The force F_(P) is determinedaccording to the following equation representing an idealizedrelationship between torque and force for a ball screw actuator:

$F_{P} = \frac{\tau_{M}2\;{\pi\eta}}{P}$where F_(P) is a force applied to the plunger 120 by the screw 332,τ_(M) is a torque applied to the screw 332, η is an efficiency of theball screw actuator 130, and P is a lead of the screw 332.1.2 Control Loop

Referring again to FIG. 1, the transdermal injection device 100 mayinclude a displacement sensor 140, an injection controller 135, and athree-phase motor controller 141. In general, the displacement sensor140 measures a displacement x(t) of the screw 332 of the ball screwactuator 130 and/or the plunger 120. The displacement sensor 140 may,for example, measure an incremental displacement of the screw 332 bystoring an initial displacement value (i.e., x(0)) and monitoring adeviation from the starting value over time. In other examples, thedisplacement sensor 140 measures an absolute displacement of the screw332 relative to a position of the displacement sensor 140 or some otherfixed reference point. In another aspect, the displacement sensor 140may be coupled to a nut or other component of a ball screw that controlslinear movement. In this configuration, the displacement sensor 140 canmeasure rotation of the screw drive, and rotational motion may becomputationally converted into linear displacement for purposes ofcontrolling operation of the device 100.

The displacement x(t) measured by (or calculated using data from) thedisplacement sensor 140 may be provided as input to the injectioncontroller 135. As is described in greater detail below, the injectioncontroller 135 processes the displacement x(t) to determine a motorcontrol signal y(t). The motor control signal y(t) is provided to thethree-phase motor controller 141 which, in conjunction with a powersupply 143, drives the rotary motor 126 according to the motor controlsignal y(t). The motor 126 causes the torque τ_(M)(t) to be applied tothe screw 332. The motor torque, τ_(M)(t) causes movement of the screw332 (or any other suitable linear actuator) in a direction along thelongitudinal axis 122.

1.3 System Diagram

Referring to FIG. 3, a schematic diagram of the system of FIG. 1 showsthe rotary motor torque τ_(M) being applied to the ball screw 130 instep 344. Application of the rotary motor torque, at a given time t₁ bythe rotary motor causes application of a force, F_(M)(t₁) to the screw332 of the ball screw 130 as shown in step 345, which in turn causes adisplacement of the screw 332 in step 348.

The displacement of the screw 332 of the ball screw 130 is measured bythe displacement sensor 140 and is fed back to the injection controller135. As is described in greater detail below, the injection controller135 processes the measured displacement to provide sensor feedback 348to determine a motor control signal y(t₁) which is supplied to thethree-phase motor controller 141. The three-phase motor controller 141drives the rotary motor 326 according to the motor control signal y(t₁),causing the motor 126 to apply a torque τ_(M)(t₂) to the screw 332 ofthe ball screw 130 at a time t₂. As is noted above, the torque τ_(M)applied to the screw 332 causes application of a force F_(P) to theplunger 120 with F_(P) being determined as:

$F_{P} = \frac{\tau_{M}2\;\pi\;\eta}{P}$where F_(P) is a force applied to the plunger 120 by the screw 332,τ_(M) is a torque applied to the screw 332, η is an efficiency of theball screw actuator 130, and P is a lead of the screw 332.

Referring to FIG. 4, in some examples the injection controller 135includes a target displacement profile 450, a summing block 452, and amotor control signal generator 454. Very generally, the injectioncontroller 135 receives a displacement value x(t) at time t from thedisplacement sensor 140. The time t is provided to the targetdisplacement profile 450, which determines a target displacement valuex_(T)(t) for the time t.

In some examples, the target displacement profile 450 includes a mappingbetween target displacement values and times associated with aninjection cycle (i.e., a range of time over which the plunger 120 of thedevice moves). For example, in the target displacement profile 450 shownin FIG. 4 the displacement starts at zero at the beginning of aninjection cycle (i.e., at time t₀) and changes (e.g., increases) overtime as the injection cycle proceeds, with each instant in time of theinjection cycle being associated with a corresponding displacementvalue. As is described in greater detail below, in some examples therate of change of the displacement values varies over time, withdifferent time intervals of the injection cycle being associated withdifferent rates of change of displacement values. Control of the plungerdisplacement, e.g., according to the target displacement profile 450,can be used to perform complex injections. For example, in one aspect,the plunger 120 is displaced relatively quickly during an initialpiercing phase to penetrate the skin barrier, and in other timeintervals the plunger 120 is displaced relatively slowly to deliver theinjectate through an opening formed during the initial, piercing phase.In another aspect, the target displacement profile 450 may controlmultiple, sequential injections each having a biphasic profile with apiercing phase and a drug delivery phase. In practice, the actualdisplacement profile of the plunger 120 may vary from the ideal targetdisplacement profile according to physical limits of the system andother constraints.

Both the measured displacement value x(t) and the target displacementvalue x_(T)(t) are provided to the summing block 452. The summing block452 subtracts the measured displacement value x(t) from the targetdisplacement value x_(T)(t) to obtain an error signal x_(E)(t). Theerror signal x_(E)(t) is provided to the motor control signal generator454 which converts the error signal to a motor control signal y(t). Themotor control signal y(t) is provided to the three-phase motorcontroller 141 or other suitable drive system, which in turn drives themotor 126 according to the motor control signal y(t).

In some examples, the rotary motor 126 may be a three-phase motor withthree windings 447 and three Hall sensors 449, each Hall sensor 449corresponding to a different one of the three windings 447. Each of thewindings 447 is wrapped around a laminated soft iron magnetic core (notshown) so as to form magnetic poles when energized with current. Each ofthe three Hall sensors 449 generates a corresponding output signal 456in response to presence (or lack of) a magnetic field in itscorresponding winding 447.

The three-phase motor controller 141 includes a switch control module445 and a switching module 448. The switching module 448 includes threepairs of switches 451 (with six switches 451 in total), each pair ofswitches corresponding to a different one of the windings 447 of therotary motor 126 and configurable to place the corresponding winding 447into electrical connection with the power supply 143 (whereby thewinding is energized) or with ground. The switch control module 445receives the motor control signal y(t) from the injection controller 135and the three Hall sensor output signals 456 as inputs and processes theinputs to generate six switch control signals 455, each switch controlsignal 455 configured to either open or close a corresponding switch 451of the switching module 448.

The above-described configuration implements a feedback control approachto ensure that a combination of the controlled torque applied to thescrew 332 of the ball screw 130 due to the motor 126 causes thedisplacement of the plunger to track the target displacement profile 450as the screw 332 is displaced.

1.4 Power Supply

Referring to FIG. 5, in some examples, the power supply includes abattery 560 (e.g., a Nickel Cadmium battery, a Nickel-Metal Hydridebattery, a Lithium ion battery, an alkaline battery, or any othersuitable battery type) configured to supply a voltage V₁ to a DC/DCconverter 562 (e.g., a boost converter). The DC/DC converter 562receives the supply voltage V₁ from the battery 560 as input andgenerates an output voltage V₂ greater than V₁. In some examples, theDC/DC converter 562 is configured to boost the supply voltage by afactor in the range of 5 to 20. While the battery 560 may berechargeable, the battery 560 may also usefully store sufficient energyfor multiple injections, such as two or more one milliliter injections,e.g., from replaceable single-dose cartridges or from a single,multi-dose cartridge.

The output voltage V₂ may be provided in parallel to a supercapacitor564 and to the switching module 448 of the three-phase motor controller141 via a diode 566. In operation, the output voltage V₂ charges thesupercapacitor 564 while the transdermal injection device 100 isinactive. When an injection operation commences, the switches 451 of theswitching module 448 close (according to the switch control signals455), connecting the windings 447 of the rotary motor 126 to thesupercapacitor 564. This results in a discharge of the supercapacitor564, causing current to flow through the windings 447 of the rotarymotor 126 and induce rotation of the rotary motor 126.

In some examples, the supercapacitor 564 includes a number ofsupercapacitors coupled together with a switching network. When thetransdermal injection device 100 is inactive, the switching network maybe configured so that the number of supercapacitors is connected inparallel for charging. When an injection is initiated, the switchingnetwork may be reconfigured so that the number of supercapacitors areserially connected for discharge. In some examples, the supercapacitor564 is configured to deliver a peak power of 200 Watts or more to theball screw 130 via the rotary motor 126.

In general, the supercapacitor may be any high-capacity capacitorsuitable for accepting and delivering charge more quickly than a batteryor other source of electrical energy. A wide variety of supercapacitordesigns are known in the art and may be adapted for use as thesupercapacitor 564 contemplated herein, such as double-layer capacitors,pseudocapacitors, and hybrid capacitors. Similarly, the supercapacitor564 may usefully include any number and arrangement of supercapacitorssuitable for delivering electrical power in an amount and at a ratesuitable for driving a rotary motor 126 of an injection device 100 ascontemplated herein.

2 Target Displacement Profile

Referring to FIG. 6, one example of a target displacement profileincludes a number of injection phases, each associated with acorresponding time interval.

A first injection phase 670 is associated with a first time intervalextending from time t₀ to time t₁. In the first injection phase 670, thetarget displacement of the plunger 120 is at a constant initial positionp₀ where the plunger 120 is engaged with the injectate in the chamber106. In this phase, the injection device 100 is generally prepared toperform an injection operation. In general, the first injection phase670 may be preceded by any number of preparatory steps or phases, suchas loading of an injectate (or a cartridge containing an injected) intothe injection device, the removal of bubbles from the injectate asnecessary or appropriate, measuring environmental conditions, measuringparameters of an injection site, and any other steps or combination ofsteps useful for performing, or preparing to perform, a needle-freeinjection as contemplated herein.

In one aspect, the rotary motor 126 may be mechanically engaged with theball screw actuator 130 (or any other suitable linear actuator) whilethe rotary motor 126 is stationary in the first injection phase 670.That is, the rotary motor 126 may be pre-engaged with the ball screwactuator 130 and preload to remove any mechanical slack in themechanical components of the system. In this configuration, a mechanicalswitch or the like may be used to prevent relative movement of thecomponents, and/or a gate or seal may be used at the nozzle exit toprevent leakage of drug from the chamber 106. In another aspect, therotary motor 126 may be slightly spaced apart from engagement with theball screw actuator 130. In this latter configuration, the rotary motor126 may usefully accelerate (while unloaded) into engagement with theball screw actuator 130 at an end of the first injection phase 670 or ata beginning of the second injection phase 672 to facilitate a greaterinitial velocity of injectate from the nozzle. This may, for example,include a single rotation of the rotary motor 126 from engagement withthe ball screw actuator 130, or a fractional rotation suitable tofacilitate very high initial rotational acceleration.

A second injection phase 672 is associated with a second time intervalextending from time t₁ to t₂. In the second injection phase 672,movement of the plunger 120 may be initiated. In this phase, the targetdisplacement of the plunger 120 increases at a relatively high firstrate to move the plunger 120 from the initial position p₀ to a firstposition p₁. In general, the motion of the plunger 120 in this phase maycause a jet of injectate to be ejected from the chamber 106 of theinjector head 104 (via the opening 114) with a first velocity V₁ atleast sufficient to pierce human tissue to a subcutaneous depth. In someexamples, the second injection phase 672 spans a time interval less than100 ms (i.e., the difference between t₁ and t₂ is less than 100 ms). Insome examples, the second injection phase 672 spans a time interval lessthan 60 ms (i.e., the difference between t₁ and t₂ is less than 60 ms).In some examples, the second injection phase 672 spans a time intervalless than 10 ms (i.e., the difference between t₁ and t₂ is less than 10ms).

More generally, the injection device 100 may be configured so that inthis second injection phase 672, the plunger 120 transitions from astationary position to the target velocity at a sufficient rate for theinitial stream of injectate to achieve a piercing velocity substantiallyinstantaneously, e.g., without substantial leakage or loss of injectateat the surface. By configuring the linear drive system described aboveto accelerate in this manner from a fixed position to a piercingvelocity, the injection device 100 may advantageously mitigate loss ofinjectate. As a further advantage, an injection device with thiscapability can usefully perform multiple sequential injections withoutrequiring any physical recharge or resetting of a mechanical storedenergy system.

A third injection phase 674 is associated with a third time intervalextending from time t₂ to t₃. In the third injection phase 674 thetarget displacement of the plunger 120 increases at a rate substantiallythe same as the first rate to move the plunger 120 from the firstposition p₁ to the second position p₂. In this third injection phase674, the plunger 120 may be moved at a rate to cause the jet ofinjectate to be ejected from the chamber 106 of the injector head 104with a second velocity V₂ greater than or equal to the first velocityV₁. While the rate of plunger 120 movement and the velocity of theinjectate stream may vary within this third injection phase 674, e.g.,according to limitations on control precision, physical systemcomponents, and so forth, the plunger 120 should generally be driven ata minimum velocity suitable for piercing tissue at a target site to adesired depth for delivery of the injectate. The jet of injectate mayalso have a maximum velocity selected to avoid over-penetration or otherundesirable tissue damage.

A fourth injection phase 676 is associated with a fourth time intervalextending from time t₃ to time t₄. In the fourth injection phase 676 thetarget displacement of the plunger 120 increases at a third rate,relatively slower than the first rate, to move the plunger 120 from thesecond position p₂ to a third position p₃. In this fourth injection 676,the injection device 100 may generally decelerate the plunger 120 tocause the jet of injectate to eject from the chamber 106 of the injectorhead 104 with a third velocity V₃ less than the first velocity V₁, whichmay generally be any velocity suitable for non-piercing delivery ofadditional injectate at a current depth of the stream of injectatewithin the target tissue.

A fifth injection phase 678 is associated with a fifth time intervalextending from time t₄ to t₅. In the fifth injection phase 678 thetarget displacement of the plunger 120 continues to increase at thethird rate to move the plunger 120 from the third position p₃ to thefourth position p₄. In the fifth injection phase 678, the injectiondevice 100 may generally deliver the injectate—typically a majority ofthe injectate in the chamber 106—at a subcutaneous depth achieved duringthe prior, piercing phase. The rate of movement may be generallyconstant, or may otherwise vary consistent with maintaining subcutaneousdrug delivery without further piercing of the tissue.

It will be appreciated that some continued piercing may occur during thefifth injection phase 678. Provided that any additional piercing doesnot create a pathway below subcutaneous depth within the target tissuethat might result in loss or misdelivery of therapeutic dosage, thenthis additional piercing will not affect the efficacy of transdermaldrug delivery. It will also be understood that the total displacement ofthe plunger 120 will control the volume of drug delivered over thecourse of an injection, and a duration of the fifth injection phase 678may correspondingly be selected according to an intended dosage.

Finally, a sixth injection phase 680 occurs after time t₅. In the sixthinjection phase 680 the target displacement of the plunger 120 stopsincreasing, substantially halting the plunger 120 at a fourth positionp₄. The sixth injection phase 680 is associated with completion of theinjection operation. As noted above, from this position, additionalinjection cycles may be initiated, provided of course that sufficientadditional drug remains in the injection device 100 for completingadditional injections.

In order to quickly achieve a piercing velocity and avoid loss of drugat the surface of an injection site, the second injection phase 672(where acceleration of the injectate occurs) may be short relative tothe piercing phase that is maintained once the piercing velocity isachieved. Thus in some examples, the time interval associated with thethird injection phase 674 is in a range of two to twenty times as longas the time interval associated with the second injection phase 672. Insome examples, the time interval associated with the second injectionphase 672 has a duration between 30 milliseconds and 100 millisecondsand the time interval associated with the third injection phase 674 hasa duration between 100 milliseconds and 1000 milliseconds.

More generally, the duration of each phase may depend on the diameter ofthe injectate stream, the properties of the injectate, thecharacteristics of the tissue at the injection site and so forth. Thus,the injection profile may usefully employ any durations suitable foraccelerating to a piercing velocity sufficiently rapidly to avoidsubstantial loss of injectate, maintaining a piercing velocity until atarget depth (e.g., subcutaneous depth) is achieved, and thenmaintaining a non-piercing velocity to deliver a full dose at the targetdepth.

It will also be understood that, while a single injection cycle isillustrated, the injection device 100 contemplated herein may usefullybe configured for multiple, sequential injections. As such any number ofinjection cycles might usefully be performed, and any suchmulti-injection applications are expressly contemplated by thisdescription.

2.1 Rotary Motor Speed

Referring to FIG. 7, in the first injection phase 670, the injectioncontroller 135 controls the rotary motor 126 to maintain its speed atsubstantially 0 rotations per minute (RPM) to ensure that the plunger120 remains stationary at the initial position p₀. This may includeactively maintaining the rotary motor 126 in a fixed position, e.g., bymonitoring the position and activation the rotary motor 126 incounter-response to any detected motion or drift, or by control amagnetic, mechanical, or electromechanical lock that securely engagesthe plunger 120 in the initial position p₀. In another aspect, this mayinclude passively maintaining the rotary motor 126 in the fixed positionby withholding control signals or drive signals from the rotary motor126. It will also be understood that combinations of the foregoing mayadvantageously be employed. For example, the plunger 120 may be lockedwith a mechanical lock during storage or while otherwise not in use, andthen the rotary motor 126 may be used to electromechanically andactively lock the position of the plunger 120 when the mechanical lockis disengaged to prepare for an injection. In this manner, power may beconserved during long term storage, while the position can be securelyand controllably locked using the rotary motor 126 in an intervalimmediately prior to injection in order to prevent, e.g., leakage of aninjectate.

In the second injection phase 672, the injection controller 135 maycontrol the rotary motor to accelerate from 0 RPM to a first rotarymotor speed S₁ (e.g., 33,000 RPM), causing the plunger 120 to move fromthe initial position p₀ to the first position p₁. In the third injectionphase 674, the injection controller 135 may control the rotary motor 126to maintain a speed at or above the first rotary motor speed S₁, causingthe plunger 120 to move from the first position p₁ to the secondposition p₂. In the fourth injection phase 676, the injection controller135 may control the rotary motor 126 to decelerate to a second rotarymotor speed S₂ (e.g., 11,000 RPM) less than the first rotary motor speedS₁, causing the plunger 120 to move from the second position p₂ to athird position p₃. In the fifth injection phase 678, the injectioncontroller 135 may control the rotary motor 126 to maintain the secondrotary motor speed S₂, causing the plunger 120 to move from the thirdposition p₃ to a fourth position p₄ at a substantially consistent ratefor delivery of an injectate at a target depth for an injection.

In the sixth injection phase, the injection controller 135 may controlthe rotary motor 126 to decelerate its speed from the second rotarymotor speed S₂ to 0 RPM, causing movement of the plunger 120 tosubstantially halt at the fourth position p₄.

While the supercapacitor 564 in the power supply 143 described above maybe used during any portion of the injection delivery, the supercapacitor564 may be particularly advantageous where high mechanical loads areanticipated, e.g., during the initial acceleration and piercing phases,as well as where necessary or helpful to quickly decelerate or stop theplunger 120, e.g., at the fourth position p₄. Thus, the supercapacitor564 may be specifically used during the second injection phase 672, thethird injection phase 674, and optionally the fourth injection phase 676if high power is required to maintain a target speed even during adeceleration of the injectate to a drug delivery velocity, and/or ifhigh power is required to quickly decelerate or stop the plunger 120.

2.2 Injectate Velocity

Referring to FIG. 8, in the first injection phase 670, no injectate isejected from the chamber 106 (i.e., the initial injectate velocity, V₀is 0 m/s). In the second injection phase 672, the injectate velocityincreases from 0 m/s to the first velocity, V₁ at least sufficient topierce human tissue. In some examples, the first velocity V₁ is at least200 m/s. If piercing is not initiated quickly, then there may besubstantial loss or leakage of drug. Thus, in some embodiments, therotary motor 126 may usefully be configured to reach the first velocityV₁ for injection from a stationary starting point in not more than threerotations, such as less than two rotations, or less than one rotation.

In the third injection phase 674, the injectate velocity may bemaintained at a second velocity V₂ greater than or equal to the firstvelocity V₁ in order to continue piercing tissue at a target site. Wherethe first velocity V₁ is a minimum velocity for piercing tissue, thenthe second velocity V₂ is preferably maintained above the first velocityV₁ in order to continue piercing throughout the third injection phase674. However, the first velocity V₁ may instead be a minimum velocity oran optimum velocity to initiate piercing, in which case the secondvelocity V₂ may usefully be any velocity greater than, equal to, or lessthan the first velocity V₁ suitable for continuing to pierce tissue tothe desired, target depth. Similarly, the second velocity V₂ may varyover the duration of the third injection phase 674 provided that thesecond velocity V₂ remains within this window of useful piercingvelocities.

In the fourth injection phase 676, the injectate velocity may decreasesto a third velocity V₃ (in a range between a maximum third velocityV_(3Max) and a minimum third velocity V_(3Min)) sufficient to deliverthe majority of the injectate in the chamber 106 at a subcutaneousdepth. In the fifth injection phase 678, the injectate velocity may besubstantially maintained at the third velocity V₃ while the majority ofthe injectate in the chamber 106 is delivered to the subcutaneous depththrough the channel created during the third injection phase 674. Itwill be appreciated that the third velocity V₃ may vary over the courseof the fifth injection phase 678 between any values—typically greaterthan zero and less than a piercing velocity—consistent with delivery ofthe injectate at the target depth. Finally, in the sixth injection phase680, the injectate velocity may decrease to 0 m/s as the injectionoperation completes.

3 Injectate

In some examples, the volume of injectate in the chamber is at least onemilliliter. Thus, in one aspect the injection device 100 may beconfigured to deliver one milliliter of drug subcutaneously in a singledose, or as a number of sequential doses over time, e.g., to differentlocations or over the course of an extended dosing schedule. Where alarge number of sequential doses are intended, or where a larger singledose is intended (e.g., more than one milliliter) the chamber mayusefully have a greater volume. For multi-dose applications, thecontents of the chamber 106 may be conveniently distributed in discretedoses using a rotary motor and linear drive system as contemplatedherein. In some examples, the volume of injectate in the chamber is lessthan or equal to approximately 0.5 milliliters. In some examples, thevolume of injectate in the chamber is less than or equal toapproximately 0.3 milliliters. In some examples, the volume of injectatein the chamber is a therapeutic amount of injectate.

In some examples, the injectate includes a biological drug. In someexamples, the injectate has a viscosity of at least three centipoise ata temperature between two degrees and twenty degrees Celsius. In someexamples, the injectate has a viscosity of about three centipoise toabout two hundred centipoise at a temperature between two degrees andtwenty degrees Celsius. Thus, the system described herein may usefullybe employed with large molecule therapeutics or other drugs havingrelatively high viscosities.

4 Miscellaneous

In one aspect, the injection controller may be configured to cause theneedle-free transdermal injection device 100 to perform a number ofsequential injection operations in close temporal proximity to oneanother. The injection device 100 may usefully be instrumented tosupport this operation by sensing movement of the injection device 100and providing tactile, visible, audible or other feedback to aid innavigating the user through a multi-injection procedure.

In another aspect, a number of sequential injection operations may beperformed without having to reverse the movement of the rotary motor(i.e., to withdraw the plunger). Thus, where additional injectateremains in the injection device 100 at the end of an injection cyclesufficient for an additional dose, the rotary motor 126 may remainstationary, and a second, complete injection cycle may be initiated fromthis new starting position. In this context, the rotary motor 126 may bemanually locked, or electromagnetically maintained in a fixed locationin order to prevent leakage or other loss of therapeutic product.

In some examples, the linkage (e.g., the ball screw linkage) isbidirectionally coupled to the rotary motor and the plunger such thatbidirectional displacement of contents in the chamber is possible, e.g.by moving the plunger toward an exit nozzle to eject contents, or movingthe plunger away from the exit nozzle to load additional drug into theinjection device 100.

In some examples, the transdermal injection device includes a sensorsystem for detecting when the device is properly positioned forperforming an injection operation. In some examples, once the device isproperly positioned, the injection controller is configured to initiatethe injection operation without any observable latency. That is, thesensor system may monitor the injection device 100, determine when theinjection device 100 is properly positioned and stationary, and theninitiate an injection. Depending on the duration and feel of theinjection, the injection may usefully be preceded by a beep, vibration,or other human-perceptible signal alerting a user that the injection isabout to occur.

In some examples, one or more conventional capacitors (e.g.,electrolytic capacitors) can be used instead of the supercapacitor.

In some examples the injection controller is configured to prevent twoor more injection operations within a predetermined minimum injectioncycle time. Thus, for example, where a dosing regimen specifies aminimum time before injections, or where an injection is being deliveredas a sequence of injections in different but adjacent locations, theinjection controller may monitor activation of the injection device 100to ensure that any rules for a corresponding injection protocol areadhered to.

In some examples, the needle-free transdermal injector head is formed asa removable cartridge for containing injectate. The removable cartridgehas an opening with a predetermined shape for ejecting the injectate ina stream with a predetermined shape. In some examples, the needle-freetransdermal injector includes a movable cartridge door mechanism. A usercan interact with the movable cartridge door mechanism to loadcartridges into the needle-free transdermal injector and to unloadcartridges from the needle-free transdermal injector.

While the above description relates primarily to methods and apparatusesfor the injection of therapeutics through human tissue to a subcutaneousdepth, it is noted that, in some examples the methods and apparatusesdescribed above are used for injection of therapeutics through humantissue to other shallower or deeper depths. For example, the methods andapparatuses can be used for a shallow injection of therapeutics into thedermis, or for a deeper injection though the subcutaneous layer of fatand connective tissue into a patient's musculature.

It is to be understood that the foregoing description is intended toillustrate and not to limit the scope of the invention, which is definedby the scope of the appended claims. Other embodiments are within thescope of the following claims.

What is claimed is:
 1. An apparatus for injectate delivery comprising: acartridge containing a volume of an injectate and an exit port; a linearactuator configured for delivery of the injectate from the exit port ofthe cartridge, the linear actuator including a linkage; a rotary motormechanically coupled to the linkage; a controller coupled to the rotarymotor; and a power supply including a direct current to direct current(DC/DC) converter disposed between a capacitive energy storage elementand the rotary motor; wherein the controller is configured to control alinear motion of the actuator in response to a control signal bycontrolling an electrical input supplied to the rotary motor in a firstinterval during which the rotary motor is engaged with the cartridge todisplace the injectate therefrom; a second interval immediatelyfollowing the first interval during which the controller drives therotary motor at a first speed selected to create a jet of the injectatefrom the cartridge with a velocity at least sufficient to pierce humantissue; a third interval during which the controller continues operatingthe rotary motor at or above the first speed in order to maintain thejet of the injectate at or above the velocity and create a channelthrough the human tissue to a subcutaneous depth; a fourth intervalduring which the controller decelerates the rotary motor to a secondspeed selected to deliver the volume of the injectate at thesubcutaneous depth.
 2. The apparatus of claim 1 further comprising asensor system configured to detect when the apparatus is properlypositioned to deliver the injectate to a patient, wherein the controllerand the rotary motor are configured to initiate delivery of theinjectate when the sensor system indicates that the apparatus isproperly positioned.
 3. The apparatus of claim 2 wherein the sensorsystem detects a contact of the apparatus with a skin of the patient. 4.The apparatus of claim 2 wherein the sensor system detects a position ofthe exit port relative to a body of the patient.
 5. The apparatus ofclaim 1 further comprising the capacitive energy storage element.
 6. Theapparatus of claim 5 wherein the capacitive energy storage elementincludes a plurality of supercapacitive energy storage elements and thepower supply is configured to switch the plurality of supercapacitiveenergy storage elements into a parallel configuration during a chargingoperation and to switch the plurality of supercapacitive energy storageelements into a serial configuration for an injection operation.
 7. Theapparatus of claim 1 further comprising the capacitive energy storageelement, the capacitive energy storage element including a plurality ofcapacitors.
 8. The apparatus of claim 7 further comprising a battery,the power supply configured to switch the plurality of capacitors into aparallel configuration with the battery during a charging operation andto switch the plurality of capacitors into a serial configuration for aninjection operation.
 9. The apparatus of claim 1 wherein the powersupply further comprises a battery and a direct current to directcurrent (DC/DC) converter disposed between the battery and thecapacitive energy storage element.
 10. The apparatus of claim 9 whereinthe DC/DC converter is configured to boost a voltage supplied by thebattery by a factor in a range of 5-20.
 11. The apparatus of claim 1wherein substantially all of the electrical input supplied to the rotarymotor during the second interval and the third interval is supplied fromthe capacitive energy storage element.
 12. The apparatus of claim 1wherein the controller is configured to prevent multiple injectatedelivery operations within a predetermined minimum injection cycle time.13. The apparatus of claim 1 wherein the third interval is in a range oftwo to twenty times as long as the second interval.
 14. The apparatus ofclaim 1 wherein the second interval has a first duration of between 30milliseconds and 100 milliseconds and the third interval has a secondduration of between 100 milliseconds and 1000 milliseconds.
 15. Theapparatus of claim 1 wherein the cartridge is configured to be removablyand replaceably coupled to the apparatus, the cartridge containing aninjectate and the cartridge including an exit port with a predeterminedshape for ejecting the injectate in a stream.
 16. The apparatus of claim15 wherein the electrical input supplied during the third interval isselected to drive the rotary motor at a speed sufficient to drive thestream from the exit port at a velocity to pierce human skin, andwherein a duration of the third interval is selected to pierce the humanskin with the stream to a subcutaneous depth.
 17. The apparatus of claim16 wherein the controller is configured to control the linear motion ofthe actuator in response to the control signal by controlling theelectrical input supplied to the rotary motor during a fifth intervalafter the fourth interval, wherein the electrical input supplied to therotary motor during the fifth interval is selected to deliver additionalinjectate from the cartridge at the subcutaneous depth.
 18. Theapparatus of claim 1 wherein, during the second interval, the controlleraccelerates the rotary motor from stationary to a first speed selectedto create a jet of the injectate from the cartridge with a velocity atleast sufficient to pierce human tissue to a subcutaneous depth.
 19. Theapparatus of claim 1 wherein the injectate is a biological drug.
 20. Theapparatus of claim 1 further comprising a plurality of supercapacitorscoupled to the rotary motor and configured to provide electrical powerto the rotary motor during the second interval, the third interval andthe fourth interval.